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Ammoscato F.,University of Rome La Sapienza | Scirocco A.,University of Rome La Sapienza | Altomare A.,Biomedical University of Rome | Matarrese P.,Instituto Superiore Of Sanita | And 9 more authors.
Neurogastroenterology and Motility | Year: 2013

Background: Lactobacillus species might positively affect gastrointestinal motility. These Gram-positive bacteria bind Toll-like receptor 2 (TLR2) that elicits anti-inflammatory activity and exerts protective effects on damage induced by lipopolysaccharide (LPS). Whether such effect occurs in gastrointestinal smooth muscle has not been established yet. Aim of this study was to characterize the effects of Lactobacillus rhamnosus GG (LGG) and of supernatants harvested from LGG cultures on human colonic smooth muscle and to explore their protective activity against LPS-induced myogenic morpho-functional alterations. Methods: The effects of LGG (ATCC 53103 strain) and of supernatants have been tested on both human colonic smooth muscle strips and isolated cells in the absence or presence of LPS obtained from a pathogenic strain of Escherichia coli. Their effects on myogenic morpho-functional properties, on LPS-induced NFκB activation, and on cytokine production have been evaluated. Toll-like receptor 2 expression has been analyzed by qPCR and flow cytometry. Key Results: Lactobacillus rhamnosus GG exerted negligible transient effects per se whereas it was capable of activating an intrinsic myogenic response counteracting LPS-induced alterations. In particular, both LGG and supernatants significantly reduced the LPS-induced morpho-functional alterations of muscle cells, i.e. cell shortening and inhibition of contractile response. They also hindered LPS-induced pro-inflammatory effects by decreasing pro-inflammatory transcription factor NFκB activation and pro-inflammatory cytokine IL-6 secretion, and restored the secretion levels of anti-inflammatory cytokine IL10. Conclusions & Inferences: Taken together these data demonstrate that LGG protects human colonic smooth muscle from LPS-induced myogenic damage and might be beneficial on intestinal motor disorders due to bacterial infection. This study provides conclusive proof of protective effect of Lactobacillus rhamnosus GG (LGG) and derived factors against LPS-induced human colonic smooth muscle alterations. In fact, this study supports the evidence that LGG interferes with the muscular inflammatory reaction triggered by infection and might reduce the risk of progression toward a postinfective disorder. Furthermore, these experimental data, obtained either on human isolated cell or muscle strips, provide a rationale to design clinical studies where the efficacy of probiotics in bacterial-related gut motor disorders would ultimately be defined. © 2013 John Wiley & Sons Ltd.


PubMed | Medical Oncology, Oncology, National Cancer Center, University of Florence and 13 more.
Type: Journal Article | Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology | Year: 2017

189 Background: A significant percentage of metastatic castration-resistant prostate cancer (mCRPC) patients (pts) progressing during or after a docetaxel (D) based therapy are candidates for additional effective treatments. Taxanes remain the mainstay of treatment for a wide range of tumours including mCRPC. Cabazitaxel, a next generation of taxane, was approved based on results from the TROPIC study (NCT00417079). Cbz plus prednisone (P) was associated with a higher overall survival than mitoxantrone (MTX) (15.1 vs 12.7 mo, HR=0.70; P<0.0001). Moreover CbzP was associated with clinical benefits, better PFS, maintenance of ECOG PS, improved tumour and PSA response, longer time to tumour and PSA progression while pain control was similar to MTX. These clear benefits supported a global EAP.Here we report, the preliminary safety analysis of 165 pts entered in the study from 25 Italian centres between Jan and Nov 2011. Pts received Cbz 25 mg/mMedian age was 70 years (21.8% of the cases were 75 years); pts with PS 0-1=98.2%; median number of previous D cycles was 8; 30.8% received 450 675 mg, 14.7% received 675 900 mg and 28.2% received 900 mg of D. Median time from last D dose to first CbzP dose was 5 months including any other eventual chemotherapy treatment. 49.1% of the pts entered in this EAP because refractory to D (PD during or within 3 months since the last D administration), overall 72 % of pts had 2 or more met sites. At the time of this analysis approximately 50% of pts received 4 cycles. A total of 68 pts discontinued CbzP due to PD (38.2%), AEs related and not related (38.2)%, Investigators decision (2.9%) or other reasons (20.6%). The most common G 3/4 AEs were neutropenia (35.2%), leukopenia (17.6%), anaemia (5.5%) febrile neutropenia (4.2%); main non-haematological AEs were asthenia (4.8%) and fatigue (4.2%).This large analysis confirms a manageable safety profile of cabazitaxel in routine clinical practice. The safety profile showed in EAP study suggests cabazitaxel a safe and effective treatment option in mCRPC pts progressing during or after a docetaxel based therapy.NCT01254279.


Ferretti A.,Azienda Ospedaliera S. Andrea | Monaco E.,Azienda Ospedaliera S. Andrea | Caperna L.,Azienda Ospedaliera S. Andrea | Palma T.,Azienda Ospedaliera S. Andrea | Conteduca F.,Azienda Ospedaliera S. Andrea
Knee Surgery, Sports Traumatology, Arthroscopy | Year: 2013

Purpose: Due to the increasing number of primary anterior cruciate ligament (ACL) reconstructions, the need for revision surgery has risen. The aim of this study was to evaluate the use of contralateral doubled semitendinosus and gracilis tendon (DGST) for revision anterior cruciate ligament reconstruction. Methods: Twelve patients undergoing revision ACL reconstruction with hamstring tendon were examined at an average follow-up of 3 years. All patients underwent a thorough subjective and objective evaluation, which included a KT-1000 arthrometric evaluation, and a radiographic examination. Results: Subjective evaluation yielded a median score of 5. 5 (range 2-9) on the Tegner activity scale. The mean Lysholm score was 95 (SD 9. 5), and the mean subjective IKDC 2000 score was 95. 4 (SD 7. 8). At physical examination, a negative Lachman test was found in ten patients; one patient had a positive Lachman test with a firm end-point, and one other patient had a clearly positive Lachman test. Two patients had a grade 1+ on pivot shift testing. Only 1 patient showed a side-to-side difference more than 5 mm at the maximum manual KT-1000 arthrometer. Three patients (25 %) showed initial signs of osteoarthritis. Conclusions: The results of the study show that the use of hamstring tendons harvested from the unaffected knee represents a valid option for revision surgery following a failed primary ACL reconstruction using DGST grafts. Level of evidence: IV. © 2012 Springer-Verlag.


Salemi S.,Azienda Ospedaliera S. Andrea | D'Amelio R.,University of Rome La Sapienza
International Reviews of Immunology | Year: 2010

Vaccine administration is a very effective tool to prevent infectious diseases, but its powerful stimulus on the immune system has generated the fear of exacerbating previously diagnosed autoimmune diseases. Such a fear is also a consequence of the generally anecdotal observation of post-vaccine autoimmune reactions in few previously healthy susceptible individuals. However, patients with autoimmune diseases have an approximately double risk than the general population of developing infections. Thus, the matter has been analyzed from a double point of view, the possible induction of autoimmunity by vaccinations in healthy people and the vaccination safety and immunogenicity in patients with autoimmune diseases. Copyright © 2010 Informa Healthcare USA, Inc.


Noto A.,University of Rome La Sapienza | De Vitis C.,University of Rome La Sapienza | De Vitis C.,University of Catanzaro | Roscilli G.,University of Rome La Sapienza | And 13 more authors.
Oncotarget | Year: 2013

Personalized therapy of advanced non-small cell lung cancer (NSCLC) has been improved by the introduction of EGFR tyrosine kinase inhibitors (TKIs), gefitinib and erlotinib. EGFR TKIs induce dramatic objective responses and increase survival in patients bearing sensitizing mutations in the EGFR intracytoplasmic tyrosine kinase domain. However, virtually all patients develop resistance, and this is responsible for disease relapse. Hence several efforts are being undertaken to understand the mechanisms of resistance in order to develop combination treatments capable to sensitize resistant cells to EGFR TKIs. Recent studies have suggested that upregulation of another member of the EGFR receptor family, namely ErbB3 is involved in drug resistance, through increased phosphorylation of its intracytoplasmic domain and activation of PI3K/AKT signaling. In this paper we first show, by using a set of malignant pleural effusion derived cell cultures (MPEDCC) from patients with lung adenocarcinoma, that surface ErbB3 expression correlates with increased AKT phosphorylation. Antibodies against ErbB3, namely A3, which we previously demonstrated to induce receptor internalization and degradation, inhibit growth and induce apoptosis only in cells overexpressing surface ErbB3. Furthermore, combination of anti-ErbB3 antibodies with EGFR TKIs synergistically affect cell proliferation in vitro, cause cell cycle arrest, up-regulate p21 expression and inhibit tumor growth in mouse xenografts. Importantly, potentiation of gefitinib by anti-ErbB3 antibodies occurs both in de novo and in ab initio resistant cells. Anti-ErbB3 mAbs strongly synergize also with the dual EGFR and HER2 inhibitor lapatinib. Our results suggest that combination treatment with EGFR TKI and antibodies against ErbB3 should be a promising approach to pursue in the clinic.


Salemi S.,Azienda Ospedaliera S. Andrea | D'Amelio R.,University of Rome La Sapienza
International Reviews of Immunology | Year: 2010

Autoimmune reactions to vaccinations may rarely be induced in predisposed individuals by molecular mimicry or bystander activation mechanisms. Autoimmune reactions reliably considered vaccine-associated, include Guillain-Barré syndrome after 1976 swine influenza vaccine, immune thrombocytopenic purpura after measles/mumps/rubella vaccine, and myopericarditis after smallpox vaccination, whereas the suspected association between hepatitis B vaccine and multiple sclerosis has not been further confirmed, even though it has been recently reconsidered, and the one between childhood immunization and type 1 diabetes seems by now to be definitively gone down. Larger epidemiological studies are needed to obtain more reliable data in most suggested associations. Copyright © 2010 Informa Healthcare USA, Inc.


Cicenia A.,University of Rome La Sapienza | Scirocco A.,University of Rome La Sapienza | Carabotti M.,University of Rome La Sapienza | Pallotta L.,University of Rome La Sapienza | And 2 more authors.
Journal of Clinical Gastroenterology | Year: 2014

Probiotics are alive nonpathogenic microorganisms present in the gut microbiota that confer benefits to the host for his health. They act through molecular and cellular mechanisms that contrast pathogen bacteria adhesion, enhance innate immunity, decrease pathogen-induced inflammation, and promote intestinal epithelial cell survival, barrier function, and protective responses. Some of these beneficial effects result to be determined by secreted probiotic-derived factors that recently have been identified as postbiotic mediators. They have been reported for several probiotic strains but most available literature concerns Lactobacilli. In this review, we focus on the reported actions of several secretory products of different Lactobacillus species highlighting the available mechanistic data. The identification of soluble factors mediating the beneficial effects of probiotics may present an opportunity not only to understand their fine mechanisms of action, but also to develop effective pharmacological strategies that could integrate the action of treatments with live bacteria.


Salemi S.,Azienda Ospedaliera S. Andrea | D'Amelio R.,University of Rome La Sapienza
International Reviews of Immunology | Year: 2010

Vaccinations have been traditionally considered a risk factor for the induction/reactivation of autoimmune diseases. A Medline search through key words "vaccinations and autoimmune diseases" from 1947 through December 2009 was conducted. Until now, vaccination effects in autoimmune diseases have only been studied in over 5000 patients. Vaccinations generally did not induce worsening of disease activity in patients with multiple sclerosis, systemic lupus erythematosus, rheumatoid arthritis, insulin-dependent-diabetes-mellitus, chronic arthritis in children, vasculitides, and myasthenia gravis, whereas immunogenicity, although protective, was generally lower than in normal controls, depending on disease severity and immunosuppressive therapy. Data are very poor on the efficacy. Copyright © 2010 Informa Healthcare USA, Inc.


Leone L.,University of Rome La Sapienza | Raffa S.,University of Rome La Sapienza | Martinelli D.,Azienda Ospedaliera S. Andrea | Torrisi M.R.,University of Rome La Sapienza | Santino I.,University of Rome La Sapienza
Future Microbiology | Year: 2015

Background: Carbapenem-resistant Klebsiella pneumoniae strains (KPC-Kp) are emerging worldwide causing different nosocomial infections including those of the urinary tract, lung or skin wounds. For these strains, the antibiotic treatment is limited to only few choices including colistin, whose continuous use led to the emergence of carbapenem-resistant KPC-Kp strains resistant also to this treatment (KPC-Kp Col-R). Aim: Very little is known about the capacity of the different strains of KPC-Kp to invade the epithelial cells in vitro. To verify if the acquisition of carbapenem-resistant and the colistin-resistant phenotypes are correlated with a different ability to infect a series of epithelial cell lines of various tissutal origin and with a different capacity to induce cellular death. Materials & methods: We used Klebsiella pneumoniae (KP), KPC-Kp and KPC-Kp Col-R strains, isolated from different patients carrying various tissue-specific infections, to infect a series of epithelial cell lines of different tissutal origin. The invasive capacity of the strains and the extent and characteristics of the cell damage and death induced by the bacteria were evaluated and compared. Conclusion: Our results show that both KPC-Kp and KPC-Kp Col-R display a greater ability to infect the epithelial cells, with respect to KP, and that the bacterial cell invasion results in a nonprogrammed cell death. © 2015 Future Medicine Ltd.


PubMed | Azienda Ospedaliera S. Andrea
Type: Journal Article | Journal: Knee surgery, sports traumatology, arthroscopy : official journal of the ESSKA | Year: 2013

Due to the increasing number of primary anterior cruciate ligament (ACL) reconstructions, the need for revision surgery has risen. The aim of this study was to evaluate the use of contralateral doubled semitendinosus and gracilis tendon (DGST) for revision anterior cruciate ligament reconstruction.Twelve patients undergoing revision ACL reconstruction with hamstring tendon were examined at an average follow-up of 3years. All patients underwent a thorough subjective and objective evaluation, which included a KT-1000 arthrometric evaluation, and a radiographic examination.Subjective evaluation yielded a median score of 5.5 (range 2-9) on the Tegner activity scale. The mean Lysholm score was 95 (SD 9.5), and the mean subjective IKDC 2000 score was 95.4 (SD 7.8). At physical examination, a negative Lachman test was found in ten patients; one patient had a positive Lachman test with a firm end-point, and one other patient had a clearly positive Lachman test. Two patients had a grade 1+ on pivot shift testing. Only 1 patient showed a side-to-side difference more than 5mm at the maximum manual KT-1000 arthrometer. Three patients (25%) showed initial signs of osteoarthritis.The results of the study show that the use of hamstring tendons harvested from the unaffected knee represents a valid option for revision surgery following a failed primary ACL reconstruction using DGST grafts.IV.

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